203. IL-1-RELATED CYTOKINE RESPONSES OF NONIMMUNE SKIN CELLS SUBJECTED TO CEES EXPOSURE WITH AND WITHOUT POTENTIAL VESICANT ANTAGONISTS.

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Blaha¹, M., Bowers, Jr.¹, W., Kohl¹, J., DuBose¹, D., Walker², J. ¹U.S. Army Research Institute of Environmental Medicine. ²U.S. Army Soldier and Biological Chemical Command, Natick, MA 01760. In Vitro & Molecular Toxicology, 13, (2), 99, (2000).

Summary: Sulfur mustard provokes an acute inflammatory response in skin. To determine if keratinocytes regulate this response and whether three potential vesicant antagonists can counteract adverse changes, specimens of EpiDerm™ (MatTek Corp., Ashland, MA), a human skin model of differentiating keratinocytes, were exposed 2 h to humidified air with or without 2-chloroethyl ethyl sulfide (CEES. 1.72-4.73 mg/L/min) with or without 10 mM niacinamide, a poly (ADP-ribose) polymerase (PARP) inhibitor, 25 uM CG59343B (calmodulin antagonist), or 8.4 mM leupeptin (cysteine protease inhibitor). After a 22 h incubation, levels of interleukin-1 alpha (IL-1α), its receptor antagonist (IL-1Ra), soluble type II receptor (sIL-1RII) and prostaglandin-E2 (PGE-2) were determined. Methylthiazole tetrazolium (MTT) viability tests and histological observations were also conducted. PGE-2 levels were abundant but unaffected by CEES regardless of antagonist pres-ence. Total amounts (media plus lysate) of IL-1α, IL-1Ra, and sIL-1RII were reduced with CEES irrespective of antagonist. CEES promoted the release of IL-1Ra. Exposure of EpiDerm to CEES in the presence of the vesicant antagonists did not improve viability or counteract histological damage. We conclude CEES de-presses total IL-1α and related cytokines, does not affect PGE-2 release, and adverse changes associated with CEES-exposed EpiDerm are not ameliorated by these particular antagonists. Dramatically increased (5- to 10-fold) release of IL-1Ra may provide a useful marker for cytotoxicity. The high level of IL-1Ra and increased release with injury suggest a primary function in down-regulating IL-1 inflammatory responses in skin.

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EpiDerm Data Sheet

EpiDerm Specifications

EpiDerm Technical References

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Applications: Cytokine expression/analysis, General research - skin, Inflammation - skin

Keywords: Antagonists, Cees exposure, Cytokines, EpiDerm, IL-1, IL-1a, Inflammation, Inflammatory, Inflammatory response, Non-immune skin cells

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